Lipid membrane fusion is an essential function in many biological processes. Detailed mechanisms of membrane fusion and the protein structures involved have been mainly studied in eukaryotic systems, whereas very little is known about membrane fusion in prokaryotes. Haloarchaeal pleomorphic viruses (HRPVs) have a membrane envelope decorated with spikes that are presumed to be responsible for host attachment and membrane fusion. Here we determine atomic structures of the ectodomains of the 57-kDa spike protein VP5 from two related HRPVs revealing a previously unreported V-shaped fold. By Volta phase plate cryo-electron tomography we show that VP5 is monomeric on the viral surface, and we establish the orientation of the molecules with respect to the viral membrane. We also show that the viral membrane fuses with the host cytoplasmic membrane in a process mediated by VP5. This sheds light on protein structures involved in prokaryotic membrane fusion.
BackgroundDespite the great burden of chronic respiratory diseases in China, few large multicentre, spirometry-based studies have examined its prevalence, rate of underdiagnosis regionally or the relevance of socioeconomic and lifestyle factors.MethodsWe analysed data from 512 891 adults in the China Kadoorie Biobank, recruited from 10 diverse regions of China during 2004–2008. Air flow obstruction (AFO) was defined by the lower limit of normal criteria based on spirometry-measured lung function. The prevalence of AFO was analysed by region, age, socioeconomic status, body mass index (BMI) and smoking history and compared with the prevalence of self-reported physician-diagnosed chronic bronchitis or emphysema (CB/E) and its symptoms.FindingsThe prevalence of AFO was 7.3% in men (range 2.5–18.2%) and 6.4% in women (1.5–18.5%). Higher prevalence of AFO was associated with older age (p<0.0001), lower income (p<0.0001), poor education (p<0.001), living in rural regions (p<0.001), those who started smoking before the age of 20 years (p<0.001) and low BMI (p<0.001). Compared with self-reported diagnosis of CB/E, 88.8% of AFO was underdiagnosed; underdiagnosis proportion was highest in 30–39-year olds (96.7%) compared with the 70+ age group (81.1%), in women (90.7%), in urban areas (89.4%), in people earning 5K–10 K ¥ monthly (90.3%) and in those with middle or high school education (92.6%).InterpretationIn China, the burden of AFO based on spirometry was high and significantly greater than that estimated based on self-reported physician-diagnosed CB/E, especially in rural areas, reflecting major issues with diagnosis of AFO that will impact disease treatment and management.
We study the problem of locating a single facility on a real line based on the reports of self-interested agents, when agents have double-peaked preferences, with the peaks being on opposite sides of their locations.We observe that double-peaked preferences capture real-life scenarios and thus complement the well-studied notion of single-peaked preferences. We mainly focus on the case where peaks are equidistant from the agents’ locations and discuss how our results extend to more general settings. We show that most of the results for single-peaked preferences do not directly apply to this setting; this makes the problem essentially more challenging. As our main contribution, we present a simple truthful-in-expectation mechanism that achieves an approximation ratio of 1+b/c for both the social and the maximum cost, where b is the distance of the agent from the peak and c is the minimum cost of an agent. For the latter case, we provide a 3/2 lower bound on the approximation ratio of any truthful-in-expectation mechanism. We also study deterministic mechanisms under some natural conditions, proving lower bounds and approximation guarantees. We prove that among a large class of reasonable mechanisms, there is no deterministic mechanism that outpeforms our truthful-in-expectation mechanism.
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